This project will 1) evaluate the angiogenic and cellular proliferative properties of EGF and FGF placed in high concentration in the posterior eye, 2) determine aging changes in Bruch's membrane that, in the presence of angiogenic factors, could predispose to subretinal neovascularization. TAF produces neovascularization but is not found in normal tissues; hence, its properties may not reflect tissue responses in the absence of malignancy. EGF and FGF are growth factors normally found in the circulation and body tissue. We hypothesize that naturally occurring growth factors such as EGF or FGF are responsible for diseases with vascular proliferation or cellular proliferation, for example: proliferative diabetic retinopathy, proliferative sickle retinopathy, or related diseases; senile macular degeneration or similar conditions; surface wrinkling retinopathy; and massive vitreous retraction. The experiments are designed to stimulate vascular and cellular proliferation with EGF or FGF to reproduce in the animal model the vascular and cellular proliferative diseases described above. For experimental purposes each growth factor is available in a gel, from which it leaks for weeks. The response of retinal glia, retinal vessels, retinal pigment epithelium, and choriocapillaris to EGF and FGF will be tested. The material will be injected through the pars plana into the vitreous or injected ab externo just external to the retinal pigment epithelium. Eyes without posterior ocular injury or eyes with injuries to Bruch's membrane or the internal limiting membrane will be used. Observation for neovascularization or cellular proliferation will be by ophthalmoscopy, fundus photography, fluorescein angiography, light microscopy, tritiated thymidine autoradiography, and correlated scanning electron microscopy and transmission electron microscopy. Human cadaver specimens will be examined to determine topographic features of aging Bruch's membrane.